Using bioelectronics to suppress inflammation

Peder Olofsson believes in the potential offered by electrical nerve stimulation as an alternative way of treating inflammatory diseases. He is refining the technique and adding to our knowledge of how the nervous system controls the immune system at molecular level.

Dr. Peder Olofsson

Specialist Doctor

Wallenberg Academy Fellow 2014

Institution:
Karolinska Institutet

Research field:
The inflammatory reflex and neural control of inflammation by electrical stimulation

Dr. Olofsson holds out a very thin metal wire, almost impossible to see with the naked eye.

“This is an electrode we use on mice when we study how electric stimulation of nerves can modulate inflammation.”

He is researching in the field of bioelectronic medicine. The field is a new one, and is rooted in the ground-breaking discovery that inflammation can be suppressed by activating specific neural reflexes, e.g. by delivering targeted electrical shocks to the longest nerve in the body, the vagus nerve. The discovery was made through experiments on mice just before the turn of the millennium by Professor Kevin Tracey, Director of the Feinstein Institute in New York.

The vagus nerve winds from the brainstem down to the abdomen. Stimulation of the nerve in the neck reduced levels of TNF (a signal substance in the immune system that triggers inflammation) in the spleen. Dr. Olofsson elaborates:

“We are dependent on neural reflexes. They regulate various bodily functions and organs, including blood pressure, the lungs and intestines. Now we know that the nervous system also controls the immune system, and can regulate inflammation via the inflammatory reflex.”

Having gained his PhD on inflammation of the blood vessels, Olofsson was eyeing interesting new lines of research into treatment of inflammation. It was then that he got to know Professor Tracey. They hit it off immediately and began working together.

After six years in New York Dr. Olofsson returned to Karolinska Institutet in Solna, north of Stockholm, in the fall of 2015. With funding from the Knut and Alice Wallenberg Foundation he is now putting together a new team for research in the field of bioelectronic medicine.

Promising results

Even as a child Olofsson knew he wanted to be a researcher. He has always enjoyed solving problems. His route to lab work was by no means marked out in advance. First he trained to be a doctor in Uppsala, eventually qualifying as an anesthetist and intensive care doctor.

“It became quite clear to me in my work that how the body copes with inflammation plays a decisive role in how the symptoms of many diseases manifest themselves. I began to do part-time research, moving on eventually to researching full time.”

An overactive immune system and inflammation play a central part in many widespread diseases such as rheumatism, asthma and cardiovascular disease. At present, treatment specifically targeting inflammation is limited, as Dr. Olofsson explains:

“Anti-inflammatory drugs, and also the new biological drugs such as TNF-blockers, often have side-effects. That was why I thought the discovery that nerve signals regulate the release of cytokine was so important. It offers potential for completely new and less expensive treatment methods in the future, with a lower risk of side-effects.”

In recent years there have been promising pilot studies on neural stimulation in humans with a view to alleviating various inflammatory diseases, including rheumatoid arthritis.

“A tiny device implanted in the neck sends electrical signals to the vagus nerve. In some cases inflammation has been dramatically reduced; but larger and more rigorous studies are needed before the efficacy of this method in humans can be confirmed.”

Karolinska University Hospital is participating in a study in which the method is being tested on Crohn’s disease, a chronic inflammation of the digestive tract. His own research is not specifically linked to these patient trials, however.

“But it is inspiring to have clinical trials in progress so nearby.”

Unexpected T-cell found

Dr. Olofsson works on the same floor as his former supervisor Professor Göran Hansson, who is researching into the correlation between atherosclerosis and the immune system. Atherosclerosis is a long-drawn-out inflammation that starts early.

“Everyone in the west has atherosclerosis from an early age. Nearly half of those people eventually die of cardiovascular disease. It would be fantastic if we could modulate neural reflexes to influence the processes involved in atherosclerosis and high blood pressure, in which inflammation also plays a key role,” Dr. Olofsson enthuses.

“The grant from the Knut and Alice Wallenberg Foundation makes all the difference. It gives me and this new field of bioelectronic medicine an opportunity to develop. It enables us to adopt the multidisciplinary approach needed to understand the fundamental mechanisms of the inflammatory reflex.”

Further down the corridor there is a lab where his research team is trying to understand the molecular, immunological and neurological mechanisms involved when the nervous system regulates inflammation.

“It’s essential to take a step back to understand the underlying biology in order to develop more targeted treatments. This also means we can expect the unexpected – like the special T-cell we found in the spleen, an immune cell that acts as a messenger between the vagus nerve and receptors in various organs. This is something we’ll now be looking into.”

In collaboration with MIT in the U.S. work is also in progress to develop electrodes and technology for nerve stimulation for use in long-term animal studies of widespread chronic diseases.

The vagus nerve contains 80,000 nerve fibers. Eventually, the research team will be able to identify and activate specific nerve fibers and understand the physiological signals. Dr. Olofsson adds:

“The pacemaker is a Swedish invention that corrects a defective nerve signal in the heart. Perhaps in the future we will be able to develop a similar device for the immune system.”

The Knut and Alice Wallenberg Foundation has since its establishment in 1917 awarded SEK 24 billion in grants, of which SEK 1.7 billion yearly in recent years, to excellent basic research and education in Sweden.